NIEHS has developed a research effort aimed at establishing mechanisms to utilize data on oncogene activation and expression, tumor suppressor gene inactivation, and dose-response studies for tumor induction in risk analysis of specific classes of chemical carcinogens. A further understanding of the effects of chemicals on these genes may help explain tissue and cell specificity of carcinogens, the stages in the multistep carcinogenic process at which carcinogens are active, the relationship between spontaneous and carcinogen-induced tumors, dose-response curves for chemical carcinogens, and animal-to-man extrapolations. The requirements of this contract are as follows: (1) to obtain tumor and/or preneoplastic tissue for analysis of oncogene activation and suppressor gene inactivation, (2) to determine tumor induction in various hybrids and backcrosses and obtain tissue for genotyping of individual animals to localize cancer susceptibility loci to specific chromosomal regions, and (3) to establish dose-response relationships for tumor induction by chemicals. The studies in this contract are designed to help accomplish several scientific objectives: (1) Compare proto-oncogene activation and tumor progression between strains of mice sensitive and resistant to lung and liver tumor induction, (2) Examine the mechanisms of tumor induction in rodents by genotoxic and non-genotoxic chemicals, and (3) Characterize tumor susceptibility loci in mouse lung and liver. Various specific tasks will be necessary to accomplish these objectives.